An intergral approach will be taken to the control of cardiovascular function by cellular processes involving membranes and ion translocation. Specific areas to be studied include: (1) neurohumoral receptor structure and linkage to ion channels, calcium binding and adenylate kinase; (2) formation of electrical junctions between cardiac cells in tissue culture; (3) spread of membrane excitation from the post synaptic membrane across the plasma membrane into the T tubular system; (4) transduction of the electrical excitation of the T tubular system to the release of calcium from the sarcomplasmic reticulum; (5) mechanism of control of the release and reaccumulation of calcium by the sarcoplasmic reticulum; (6) active extrusion of calcium from smooth muscle; effect of polyvalent ionophores and other drugs on membrane function in heart, smooth muscle, and the intact animal. The depth of these studies will run the gamut from the molecular aspects of membrane- ion interaction to the ultimate impact of basic cellular processes on the cardiovascular parameters of living animals. Some of the techniques which will be employed are isolation of postsynaptic membranes, electron microscopic morphological examination of tissue preparations including freeze cleavage and freeze etch, fluorescent membrane probes, rapid kinetic measurements, biochemical analysis of tissue components and measurements of hemodynamic parameters on whole animals. The ultimate goal of these studies is the development of new therapeutic approaches to alleviation of pathological conditions of the cardiovascular system.